Beneficial Metabolic Effects of 2′,3′,5′-tri-acetyl-N6- (3-Hydroxylaniline) Adenosine in the Liver and Plasma of Hyperlipidemic Hamsters

BACKGROUND: Pharmaceutical research of hyperlipidemia has been commonly pursued using traditional approaches. However, unbiased metabonomics attempts to explore the metabolic signature of hyperlipidemia in a high-throughput manner to understand pathophysiology of the disease process. METHODOLOGY/PRINCIPAL FINDINGS: As a new way, we performed (1)H NMR-based metabonomics to evaluate the beneficial effects of 2',3',5'-tri-acetyl-N(6)- (3-hydroxylaniline) adenosine (WS070117) on plasma and liver from hyperlipidemic Syrian golden hamsters. Both plasma and liver profiles provided a clearer distinction between the control and hyperlipidemic hamsters. Compared to control animals, hyperlipidemic hamsters showed a higher content of lipids (triglyceride and cholesterol), lactate and alanine together with a lower content of choline-containing compounds (e.g., phosphocholine, phosphatidylcholine, and glycerophosphocholine) and betaine. As a result, metabonomics-based findings such as the PCA and OPLS-DA plotting of metabolic state and analysis of potential biomarkers in plasma and liver correlated well to the assessment of biochemical assays, Oil Red O staining and in vivo ultrasonographic imaging suggesting that WS070117 was able to regulate lipid content and displayed more beneficial effects on plasma and liver than simvastatin. CONCLUSIONS/SIGNIFICANCE: This work demonstrates the promise of applying (1)H NMR metabonomics to evaluate the beneficial effects of WS070117 which may be a good drug candidate for hyperlipidemia

Spatial Autoregressive Coding for Graph Neural Recommendation

Graph embedding methods including traditional shallow models and deep Graph Neural Networks (GNNs) have led to promising applications in recommendation. Nevertheless, shallow models especially random-walk-based algorithms fail to adequately exploit neighbor proximity in sampled subgraphs or sequences due to their optimization paradigm. GNN-based algorithms suffer from the insufficient utilization of high-order information and easily cause over-smoothing problems when stacking too much layers, which may deteriorate the recommendations of low-degree (long-tail) items, limiting the expressiveness and scalability. In this paper, we propose a novel framework SAC, namely Spatial Autoregressive Coding, to solve the above problems in a unified way. To adequately leverage neighbor proximity and high-order information, we design a novel spatial autoregressive paradigm. Specifically, we first randomly mask multi-hop neighbors and embed the target node by integrating all other surrounding neighbors with an explicit multi-hop attention. Then we reinforce the model to learn a neighbor-predictive coding for the target node by contrasting the coding and the masked neighbors' embedding, equipped with a new hard negative sampling strategy. To learn the minimal sufficient representation for the target-to-neighbor prediction task and remove the redundancy of neighbors, we devise Neighbor Information Bottleneck by maximizing the mutual information between target predictive coding and the masked neighbors' embedding, and simultaneously constraining those between the coding and surrounding neighbors' embedding. Experimental results on both public recommendation datasets and a real scenario web-scale dataset Douyin-Friend-Recommendation demonstrate the superiority of SAC compared with state-of-the-art methods.Comment: preprin

The Effect of Calcium and Phosphorous on Growth, Feed Efficiency, Mineral Content and Body Composition of Brown Marbled Grouper (Epinephelus Fuscoguttatus) Juvenile

The objectives of this study were to know concentration of calcium (Ca) and posphorus (P) in feed for growth, feed efficiency, proximate composition of the body and mineral content of brown marbled grouper juvenile. The study was conducted in the Center for Brackiswater Aquaculture Development, Takalar with randomized completed design 6 x 3 with the treatment of Ca and P supplement in feed i.e., (A) the supplement of 0 g/kg Ca and 0 g/kg P, (B) the supplement of 6 g/kg Ca and 0 g/kg P, (C) the supplement of 0 g/kg Ca and 6 g/kg P, (D) the supplement of 6 g/kg Ca and 6 g/kg P, (E) the supplement of 12 g/kg Ca and 6 g/kg P, and (F) the supplement of 18 g/kg Ca and 6 g/kg P. The result showed that P supplement with doses of 6 g/kg and Ca of 0 g/kg in feed are significantly affects on relative growth, feed efficiency, proximate composition and mineral content of brown marbled grouper juvenile

Sterological analysis of podocyte mitochondria in adriamycin nephropathy rats

Objective: To disclose the relationship between mitochondrial morphology, density and pro-teinuria in adriamycin nephropathy rats. Method: Thirty Sprague Dawley rats of clean grade were divided into adriamycin group and control group. In adriamycin nephropathy group, rats were given adriamycin at dosage of 0.7 mg /100 g body weight by tail vein injection. The control rats received equal volume of sa-line. At 2 weeks (control group = 3, adriamycin group = 3) , 4 weeks (control = 3, adriamycin group =6) and 6 weeks (control = 8, adriamycin group = 7) after adriamycin injection, the rats were sacrificed and kidneys were harvested for preparation of ultra-thin sections. Electron microscopy was performed, and podocyte mitochondrial morphology was observed. Sterological analysis was performed on morphology and density of mitochondria in podocytes. Results: 4 weeks after adriamycin injection, the rats developed proteinuria until 6 weeks. Mitochondria in the podocytes from control rats showed ellipsoid shape. Differ-ent shaped and sized mitochondria were observed in podocytes of the adriamycin nephropathy rats. No sig-nificant statistical difference was revealed in the mitochondrial area, circumference, form factor and aspect ratio between adriamycin and control groups. Before development of proteinuria, the mitochondrial density increased significantly at 2 weeks after adriamycin injection compared with that in control rats (0.17±0.00 vs. 0.14±0.01, t = 6.173, P < 0.01). Meanwhile, the surface density of mitochondria showed an increasing trend (0.78±0.03 vs. 0.71±0.04, t =-2.526, P = 0.065). 6 weeks after adriamycin injection, the surface density of mitochondria decreased significantly compared with that in the control rats (0.71±0.11 vs. 0.87±0.12, P = 0.02) , the density of mitochondria did not change significantly. Conclusions Dysmorphic mitochondria are involved in the development of proteinuria in adriamycin ne-phropathy. The increase of mitochondrial density is an early event in the development of proteinuria. De-crease of mitochondria surface density is involved in podocyte injury and development of adriamycin ne-phropathy rats

County development and sustainability in China: a systematic scoping of the literature

Despite the importance of research and innovation in facilitating sustainable county development in China, little evidence is available concerning the output and characteristics of that research. This scoping review assesses key features or characteristics of the research output, the extent to which researchers engage with concepts of sustainability and the potential impact of the research. Publications were identified and classified using a process consistent with Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). The R programming packages igraph and wordcloud respectively were used to analyse and graphically depict the strength of authorship networks and keyword frequency. Findings revealed that this field of research is an evolving one with a widely-dispersed network of researchers increasingly using new keywords. The implications of the review findings for improving the value and impact of sustainable county development research are explored

ROS-Dependent Activation of Autophagy through the PI3K/Akt/mTOR Pathway Is Induced by Hydroxysafflor Yellow A-Sonodynamic Therapy in THP-1 Macrophages

Monocyte-derived macrophages participate in infaust inflammatory responses by secreting various types of proinflammatory factors, resulting in further inflammatory reactions in atherosclerotic plaques. Autophagy plays an important role in inhibiting inflammation; thus, increasing autophagy may be a therapeutic strategy for atherosclerosis. In the present study, hydroxysafflor yellow A-mediated sonodynamic therapy was used to induce autophagy and inhibit inflammation in THP-1 macrophages. Following hydroxysafflor yellow A-mediated sonodynamic therapy, autophagy was induced as shown by the conversion of LC3-II/LC3-I, increased expression of beclin 1, degradation of p62, and the formation of autophagic vacuoles. In addition, inflammatory factors were inhibited. These effects were blocked by Atg5 siRNA, the autophagy inhibitor 3-methyladenine, and the reactive oxygen species scavenger N-acetyl cysteine. Moreover, AKT phosphorylation at Ser473 and mTOR phosphorylation at Ser2448 decreased significantly after HSYA-SDT. These effects were inhibited by the PI3K inhibitor LY294002, the AKT inhibitor triciribine, the mTOR inhibitor rapamycin, mTOR siRNA, and N-acetyl cysteine. Our results demonstrate that HSYA-SDT induces an autophagic response via the PI3K/Akt/mTOR signaling pathway and inhibits inflammation by reactive oxygen species in THP-1 macrophages

Risk of Pneumonia in New Users of Cholinesterase Inhibitors for Dementia

To compare the risk of pneumonia among older patients receiving donepezil, galantamine, or rivastigmine for dementia